Overexpression of E2F1 promotes tumor malignancy and correlates with TNM stages in clear cell renal cell carcinoma.
Overexpression of E2F1 promotes tumor malignancy and correlates with TNM stages in clear cell renal cell carcinoma.
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E2F1 过度表达促进肿瘤恶性并与透明细胞肾细胞癌的 TNM 分期相关
DOI：
10.1371/journal.pone.0073436
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Ma X;Gao Y;Fan Y;Ni D;Zhang Y;Chen W;Zhang P;Song E;Huang Q;Ai Q;Li H;Wang B;Zheng T;Shi T;Zhang X
背景转录因子E2 F1对多种类型的癌症发挥作用。E2 F1作为一系列基因的上游调控因子，可以触发多种异常转录过程，这些过程可能主导恶性肿瘤的发生。肾透明细胞癌（Clear cell renal cell carcinoma，ccRCC）是肾细胞癌中最常见的亚型，恶性程度高，临床上缺乏生物标志物。本研究旨在探讨E2 F1在肾细胞癌中的作用及其与临床病理参数的关系。方法/主要发现转录因子E2 F1主要分布在癌细胞核中，72例肾透明细胞癌（ccRCC）组织中的mRNA表达与癌旁肾组织相比显著增加（p<0. 001）。蛋白表达与mRNA表达一致。92例E2 F1 mRNA表达与肿瘤直径、Fuhrman分级、pT分期、TNM分期分组及大血管浸润（MAVI）等病理参数相关。这些手术标本具有高级别肿瘤，伴有E2 F1表达升高。此外，E2 F1转染被发现显着有助于癌细胞的增殖，迁移和侵袭在体外。结论/意义E2 F1的过度表达可能是ccRCC局部和血管浸润的关键事件，由基质金属蛋白酶（MMP）2和MMP 9的活化指示。这些发现强调了E2 F1在转移过程中的功能的意义。此外，E2 F1在ccRCC中的临床相关性指出了潜在的新治疗靶点。
Background Transcription factor E2F1 exerts effects on many types of cancers. As an upstream regulator of a host of genes, E2F1 can trigger diverse aberrant transcription processes that may dominate malignancy. Clear cell renal cell carcinoma (ccRCC) is the most common subtype in renal cell carcinoma which displays high malignancy and has a shortage of biomarkers in clinics. Our study aimed to explore the function of E2F1 in ccRCC and its correlation with clinicopathological parameters. Methodology/Principle Findings Transcription factor E2F1 was mainly distributed in cancer cell nucleus and mRNA expression significantly increased in 72 cases of clear cell renal cell carcinoma (ccRCC) tissues compared with adjacent non-cancerous kidney tissues (p<0.001). The protein expression was consistent with mRNA expression. Further analysis in 92 cases indicated that E2F1 mRNA level expression was associated with the tumor pathologic parameters embracing diameter, Fuhrman tumor grade, pT stage, TNM stage grouping and macrovascular infiltration (MAVI). These surgical specimens had high grade tumors accompanied with an elevated E2F1 expression. Moreover, E2F1 transfection was found to contribute significantly to cancer cell proliferation, migration and invasion in vitro. Conclusions/Significance Overexpression of E2F1 may be a key event in the local and vascular infiltration of ccRCC indicated by the activation of matrix metalloproteinase (MMP) 2 and MMP9. These findings highlighted the implication of E2F1’s function in the metastatic process. Furthermore, the clinical relevance of E2F1 in ccRCC pointed to a potential new therapeutic target.
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影响因子：
--
作者：
Myong NH
通讯作者：
Myong NH
E2F1 和 Smac/DIABLO 之间的新联系：促凋亡 Smac/DIABLO 被 E2F1 转录上调
影响因子：
14.9
作者：
Xie W;Jiang P;Miao L;Zhao Y;Zhimin Z;Qing L;Zhu WG;Wu M
通讯作者：
Wu M
影响因子：
3.4
作者：
Evangelou, K.;Kotsinas, A.;Gorgoulis, V. G.
通讯作者：
Gorgoulis, V. G.
影响因子：
--
作者：
Jung M;Ramankulov A;Roigas J;Johannsen M;Ringsdorf M;Kristiansen G;Jung K
通讯作者：
Jung K
影响因子：
11.2
作者：
Johnson JL;Pillai S;Pernazza D;Sebti SM;Lawrence NJ;Chellappan SP
通讯作者：
Chellappan SP